Because of the richness of the information available from NMR, it has often been argued that NMR is the most powerful analytical technique for molecular structure determination. However, NMR has been more successful with liquids or materials dissolved in solvents than with rigid solids. The basic problem in NMR of solids is that rapid molecular tumbling and diffusion are not naturally present to average out chemical shift anisotropy and dipolar couplings of abundant spin nuclides. Hence, the lines are normally broad and unresolved (often hundreds of ppm in width). A large number of techniques have been developed to improve the resolution in NMR of solids, but most modern techniques include extremely rapid spinning of the sample at the “Magic Angle” (the zero of the second Legendre polynomial, 54.7°) with respect to B0. If the rotational rate is fast compared to chemical shift anisotropies and dipolar couplings (in units of Hz), the resolution is dramatically improved—often by two or three orders of magnitude. Even when the spinning is not fast enough to satisfy the above conditions, substantial improvements in resolution are generally obtained from the combination of MAS and multiple-pulse methods. Similar resolution problems are encountered in liquids of inhomogeneous systems, as in tissues and the mixtures of liquids and solids, because of susceptibility variations throughout the material. Here, relatively slow MAS is often effective in improving the spectral resolution of the liquid species by several orders of magnitude.
In U.S. Pat. No. 4,511,841, Bartuska discloses a modified Beams-type Bernoulli out-flow drive for MAS; and in his later U.S. Pat. No. 4,940,942, he discloses a method of improving its axial stability and providing variable temperature operation for the sample. In U.S. Pat. No. 5,508,615, I disclose a method of suppressing whirl instability in the radial bearings at very high surface speeds in MAS and improving the stability of balanced axial hydrostatic bearings, similar to the one used in U.S. Pat. No. 5,202,633. In PCT IB2005/05338, U.S. Pat. No. 7,170,292, we disclose a novel Bernoulli inflow axial bearing that is particularly advantageous for MAS when a ceramic dewar is required between the rotor and the sample coils or when the spinner needs to be hermetically sealed for operation inside an external region evacuated to high vacuum.
The progress in increasing sensitivity in NMR has been impressive over the past five decades—three to five orders of magnitude, depending on the application. The most significant, generally applicable contribution to increasing the signal to noise ratio, S/N or SNR, in the past decade has been the introduction of cryoprobes for homogeneous liquid samples, such as that by Marek, U.S. Pat. No. 6,677,751 B1, in which the receiver coil, critical tuning elements, and preamps are cryogenically cooled while the sample is kept at some experimentally desired temperature, usually near room temperature (RT). Using high-purity aluminum coils and single-layer capacitors near 25 K with the preamps perhaps at 80 K, the S/N may be increased on one or more channels in a multi-resonant probe for liquid samples by typically a factor of three to four.
Most modern NMR applications are directed at structure determinations of complex macromolecules, where it is often desirable to utilize a probe with high S/N at two or three different frequencies simultaneously, most often 1H/13C/15N, and perhaps additionally be able lock the field on the 2H resonance. High-resolution (HR) NMR probes, in which the sample tube is aligned with the polarizing field, B0, with the sample coil and other circuit elements at cryogenic temperatures, are widely used for improved S/N for liquid samples. In these probes, the sample coils are in an evacuated region for heat insulation reasons; but probes for liquids NMR do not include a sample spinner, and their rf sample coil voltages need not be very high. We are aware of no evidence that NMR probes for solid samples have ever utilized rf coils in vacuum.
Using the same coil (or coils) for both transmit and receive has been the preferred approach in NMR spectroscopy probes, both for liquids and solids, for at least three decades. In this case, Hoult's principle of reciprocity, which at least in its popular usage states that the NMR S/N during reception is, among other things, proportional to the square root of the circuit efficiency for generating a transverse rf magnetic field within the sample during transmit, has seldom been challenged.
Reciprocity, as defined above, fails to be valid when the various loss mechanisms (sample, sample coil, capacitors, shields, etc.) are at significantly different temperatures, as the transmit efficiencies are determined by the various resistances in the circuit, but the noise power during receive is proportional to both the resistance and its temperature. Hence, reciprocity fails in cryoprobes, such as that disclosed in U.S. Pat. No. 5,508,613, where the sample and perhaps some other minor loss components are much warmer than the sample coil. In U.S. Pat. No. 7,151,374, I disclose another case in which reciprocity fails—when the sample coil is not cooled, but other critical circuit components are—that is practical in high field narrow bore magnets.
In patent application publication U.S. Pat. No. 7,282,919, we disclose the first CryoMAS probe for use in wide-bore magnets, where the RT shim bore is typically 73 mm, that permits substantial improvements in S/N in triple-resonance HR MAS NMR in high field magnets without cooling the sample. This referenced prior art has a number of deficiencies: (1) the foam and fibrous materials required for thermal insulation lead to unacceptable outgassing and rapid degradation of the hi-Q hi-voltage rf components from cryodeposits; (2) the rf circuitry voltages are limited by corona and arcing (in the pressurized helium cold zone) to about 1500 V, which is not sufficient for the rf field strengths needed for many applications in NMR of solids; (3) an exceptionally large cryocooler, requiring ˜10 kW of mains power, is required to achieve the temperature needed (˜25 K) for the desired high gain in S/N and high stability of the Q; (4) the electret enhanced tribo-electric spin rate detection has very poor sensitivity when used with zirconia ceramic and the instability of the signal makes automatic closed loop control of the spin rate extremely difficult to achieve; (5) very high thermal strain is unavoidable in the ceramic spinner dewar, which makes it difficult to achieve reliability of its vacuum seals; and (6) the large first-stage heat leaks require an inconveniently large first-stage (90 K) cooling loop and a complex defrost system.
This instant disclosure provides effective solutions to the above problems in the prior art and simultaneously reduces overall manufacturing complexity and cost. The inventive design is readily compatible with triple-resonance plus lock, extended-range variable temperature operation, automatic sample exchange, and commonly available closed-cycle cold fingers.
The key to the innovation is the discovery that it is possible to make a ceramic/metallic spinner assembly that simultaneously satisfies the requirements of hermeticity, low total emissivity, rf compatibility, spinning performance, magnetic compatibility, and high filling factor by utilizing metal construction except for the central region near the rf sample coils. Hence, it is possible to maintain high vacuum in the region external to the novel MAS spinner assembly even over a very broad range of bearing and drive gas temperatures.
The instant invention, like the prior art CryoMAS, utilizes multiple rf sample coils to allow more effective minimization of sample losses, as discussed in “Using a cross-coil to reduce RF heating by an order of magnitude in triple-resonance multinuclear MAS at high fields”, J. Magn. Reson., 2006, 182, 239-253, by F. D. Doty, J. Kulkarni, C. Turner, G. Entzminger, and A. Bielecki. This is essential for minimization of sample noise and hence for maximum S/N.
The benefits of operating high-voltage components in high vacuum, are well known. While the breakdown voltage decreases by more than two orders of magnitude as the gas pressure is reduced from standard atmospheric pressure to about 1 Torr for gaps of ˜6 mm at zero magnetic field, as the pressure is further reduced, the breakdown voltage increases. At zero field, the breakdown at pressures below ˜20 mTorr may be an order of magnitude greater than at one atmosphere. The breakdown voltage in low pressure helium at high magnetic fields can be two orders of magnitude lower than for nitrogen at similar pressure and zero magnetic field. While pressure below 50 mTorr may be sufficient for some applications, successful operation of high-voltage rf circuits in a vacuum in high magnetic field where the primary residual gas is helium often requires pressure below 2 mTorr. Achieving this level of vacuum in a complex rf zone that houses an MAS sample spinner (especially one that must operate over a wide range of temperatures) and must be pumped via a flexible evacuation hose at least 5 m long has previously been perceived to be impractical.
We have discovered that seals between soft copper alloys of acceptably low magnetism (<5E-5 volumetric SI units) and some ceramics, including zirconia and silicon nitride, made using high-strain, high-strength epoxy between overlapping thin-walled cylinders of minimal clearance can achieve sufficient hermeticity (helium leak rates below 1E-7 std-cc/s) and mechanical robustness over the temperature range of at least 80-400 K, as desired for the NMR sample temperature range. When the metallic cylinder is outside the ceramic cylinder in the joint, both the epoxy and the ceramic in the lap joint experience primarily compressive stresses at temperatures below the temperature at which the epoxy was cured. Brittle materials are much less likely to fail under compressive stress than under tensile stress. Helium leak rates smaller than 1E-7 std-cc/s could further enhance performance and reliability, and leak rates as large as 1E-4 std-cc/s could sometimes be acceptable.
The benefits of operating cryogenic components in high vacuum to minimize convective heat loss are also well known, but elimination of convective heat loss is not sufficient for acceptably low heat load. The emissivity of warm ceramics, as required in the central portion of the hermetic MAS spinner assembly, is typically greater than 0.8. This would lead to an unacceptable heat load on the second-stage (˜25 K) cold finger if the ceramic surface area was not quite small. A novel spinner design allows hermetic sealing between metallic manifold components and the central ceramic components of minimal surface area. The ceramic and plastic spinner assembly and sleeve components in the prior art CryoMAS spinner assembly had external surface area greater than 30 cm2, while the novel hermetic spinner design typically has non-metallic external surface area less than 15 cm2.
Various structural and ducting components within the vacuum zone may be warm (200-400 K) without leading to excessive thermal background radiation (and cooling costs) if their surfaces have emissivity below 0.05. Moreover, their contribution to circuit noise may be acceptably small if care is taken to minimize rf eddy currents induced in them and if their surfaces have high electrical conductivity, such as gold flash (˜0.2 microns) over silver plate.
For maximum S/N benefit, it is necessary to utilize ultra-high-Q capacitors that handle high voltages (greater than 2 kV, preferably 4 kV) and tolerate repeated thermal cycling. In addition, for effective conductive cooling of the sample coil, it is necessary to utilize a dielectric of high thermal conductivity. The coaxial sapphire capacitors disclosed in the prior art CryoMAS patent and publications suffer from extremely high E-field concentrations at the ends of the outer copper sleeve, which makes it difficult to exceed 1500 V breakdown. Disc capacitors are found to have much lower E-field concentrations at the edges of the electrodes for similar dielectric thickness and voltage. The standard low-loss ceramic capacitor dielectrics have thermal conductivity in the range of 1.5 to 8 W/m-K at temperatures in the range of 20 to 40 K. We find no evidence to suggest that high-voltage disc capacitors made using a dielectric of high thermal conductivity (such as alumina, beryllia, magnesia, silicon nitride, aluminum nitride, or single-crystal quartz, all of which have thermal conductivity greater than 15 W/m-K at temperatures between 20 and 40 K) have ever been used in an NMR probe. We also find no evidence that copper-electrode ceramic disc capacitors have ever been used in NMR probes. High-grade alumina (>95%) is a particularly advantageous dielectric, as it has extremely low RF dielectric loss, exceptionally high thermal conductivity in the 20-40 K range, is mechanically robust, is not toxic, and may be copper plated by proven methods.
Cryodeposits (of solid water, nitrogen, oxygen, argon, CO2, etc.) build-up over time on cold surfaces that are not in nearly perfect vacuum. The cryodeposits severely degrade the high-voltage dielectric properties of low-loss dielectrics, and they greatly increase the emissivity of bright metals. The problem is more severe when the cold zone contains warm surfaces, especially of softer materials, that have not been carefully outgased at elevated temperature. The need for plastics and foamed and fibrous materials in the prior art pressurized CryoMAS exacerbated the rate of buildup of cryodeposits. Sufficient thermal insulation in the instant invention is obtained using radiation shields, cooled by a first-stage cooler to an intermediate temperature, between the warm components and the cold components. With a radiation shield, the external boundaries of the vacuum zone that contains the cold electronics and the hermetically sealed spinner assembly may be at RT. The outgassing and cryodeposits may be minimized if the vacuum zone is made compatible with a vacuum bake-out at an elevated temperature.